Type Intraductal Papillary Mucinous Neoplasms Research Articles

Comparison with surgically resected mucinous cystic neoplasm of pancreas and branch-duct type intraductal papillary mucinous neoplasm considering clinico-radiological high-risk features: a reassessment of current guidelines.

To perform a comparative analysis of surgically resected mucinous cystic neoplasm (MCN) of pancreas and branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) considering clinico-radiological high-risk predictors for malignant tumors using the current management guidelines. 224 patients who underwent surgical resection and had histopathologically confirmed MCNs (benign 73; malignant 17) or BD-IPMNs (benign 110; malignant 24) and had pre-operative CT or MRI were retrospectively reviewed. Tumors classified as either high-grade dysplasia or invasive carcinoma were considered malignant, whereas those with low-grade dysplasia were considered benign. Imaging features were analyzed by two radiologists based on selected high-risk stigmata or worrisome features proposed by prevalent guidelines except tumors with main pancreatic duct dilatation (> 5mm) were excluded. MCNs and BD-IPMNs showed significant differences in aspects like tumor size, location, the presence and size of enhancing mural nodules, the presence of wall or septal thickening, and multiplicity. Multivariate analyses revealed tumor size (OR, 1.336; 95% CI, 1.124-1.660, p = 0.002) and the presence of enhancing mural nodules (OR, 67.383; 95% CI, 4.490-1011.299, p = 0.002) as significant predictors of malignant MCNs. The optimal tumor size differentiating benign from malignant tumor was 8.95cm, with a 70.6% sensitivity, 89% specificity, PPV of 27.6%, and NPV of 96.9%, demonstrating superior specificity than the guideline-suggested threshold of 4.0cm. For malignant BD-IPMNs, the presence of enhancing mural nodules (OR, 15.804; 95% CI, 4.439-56.274, p < 0.001) and CA 19 - 9 elevation (OR, 19.089; 95%CI, 2.868-127.068, p = 0.002) as malignant predictors, with a size of enhancing mural nodule threshold of 5.5mm providing the best malignancy differentiation. While current guidelines may be appropriate for managing BD-IPMNs, our results showed a notably larger optimal threshold size for malignant MCNs than that suggested by current guidelines. This warrants reconsidering existing guideline thresholds for initial risk stratification and management of MCNs.

Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia: A pilot study

ObjectivesIntraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs. MethodsThis is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis. ResultsIn total, 46 patients, 48% females, mean age (range) 67 years (45–82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas. ConclusionIntraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.

Middle segment preserving pancreatectomy for branch type intraductal papillary mucinous neoplasms in the pancreatic head and tail-A case report-

症例は，79歳女性．膵頭部・膵尾部に分枝型膵管内乳頭状粘液産生腫瘍（IPMN）と診断され，手術かつインスリン自己注射導入回避を希望された．造影CTによる膵ボリューメトリーを施行，約26％（12.7cm3）の膵体積温存をシミュレーションし，脾臓動静脈温存中央区域温存膵切除を施行，病変根治切除並びに糖尿病発症を回避できた症例である．複数の膵病変が発見された際，中央区域温存膵切除は，膵機能温存のための有用な術式選択肢となりうる．文献的考察を加えて報告する．

Diabetes in intraductal papillary mucinous neoplasm of the pancreas and its association with malignancy.

Intraductal papillary mucinous neoplasms (IPMNs) have the potential to become malignant. Few studies have focused on the prevalence of the diabetes mellitus (DM) in IPMNs and its association with malignancy. We evaluated the association between DM and malignant IPMNs in this study. A total of 226 patients with pathologically confirmed IPMNs were included. Demographic data, serum biochemical data, and imaging findings were collected. The malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma. The association between DM and malignant IPMNs was studied using logistic regression analysis. The prevalence of DM was 17.7% for all type IPMNs and 31.7% for malignant IPMNs. Compared to patients without DM, those with DM had a 3.6-fold (odds ratio [OR]: 3.62; 95% confidence interval [CI]: 1.26-10.44) higher risk of invasive carcinoma and 2.5-fold (OR: 2.48; 95% CI: 1.06-5.77) higher risk of malignant IPMNs. Similar results were observed in main pancreatic duct (MPD) involved IPMNs. New-onset DM was associated with a 4.13-fold (OR: 4.13, 95% CI: 1.27-13.36) higher risk of invasive carcinoma. DM is associated with a higher risk of malignant IPMNs and invasive carcinoma, especially in patients with MPD-involved IPMNs.

Nomogram to predict malignancy in branch duct type intraductal papillary mucinous neoplasms.

Prediction of malignancy in branch duct (BD)-type intraductal papillary mucinous neoplasms (BD-IPMNs) is difficult. In this retrospective study, we showed the performance of imaging biomarker and biochemical biomarker in identifying the malignant BD-IPMNs. A total of 97 patients with pathological proved BD-IPMNs were included in this study. Imaging data were collected from magnetic resonance imaging (MRI). Malignant BD-IPMNs were defined as those with high grade dysplasia and invasive carcinoma. There were 10 patients with malignant BD-IPMNs (10.3%). Significant difference was found in prevalence of mural nodule and tumor size >3.0 cm between patients with and without malignant BD-IPMNs (44.4% vs 3.1%, P < .01; 80.0% vs 33.3%, P < .01). Significant differences were observed in mural nodule and elevated carbohydrate antigen 19-9 (CA19-9) between patients with and without invasive carcinoma (40.0% vs 7.6, P = .05; 60% vs 15.3%, P = .04). Mural nodule and tumor size >3.0 cm were the independent associated factor for malignant BD-IPMNs. The odds ratio (OR) was 5.22 (95% confidence interval [CI]: 1.04–31.16) for mural nodule and was 6.80 (95% CI: 1.16–39.71) for cyst size >3.0 cm. The combined model of mural nodule and tumor size showed good performance in identifying malignant BD-IPMNs (area under the curve [AUC] = 0.82, 95%CI: 0.67–0.97). Our data show that mural nodule and cystic size can be used as predictor of malignancy in BD-IPMN. The predictive performance is acceptable.

Syndrome de RESLES iatrogène aux antipsychotiques

Intraductal papillary mucinous neoplasms (IPMNs) constitute a group of rare conditions with a potential for malignant degeneration. The appearance of symptoms should suggest degeneration. This case demonstrates an unusual case of a patient presenting an intestinal type IPMN that was revealed by a large abdominal mass.47-year-old woman with a history of hydatid cyst of the liver. The patient was admitted to our hospital for management of large abdominal mass measuring 185 × 128*190 mm. Intra-operative findings showed a voluminous tumor, of approximately 20 cm in all its dimensions, with double solido-cystic component at the expense of the neck and the body of the pancreas. The patient underwent splenopancreatectomy. The histopathological examination confirmed the presence of intestinal type of IPMN of pancreas.Acute pancreatitis is revealed in the majority of cases of IPMNs, related to duct obstruction by secreting mucus plug. IPMNs are rarely the cause of a large abdominal mass. They are cystic lesions of slow evolution, macroscopically visible and rarely macrocystic, unlike serous cystadenoma. The tumor size is a powerful indicator of the malignancy of IPMNs. The current definitive and ideal treatment for main duct and mixed type IMPNs is a surgical resection.IPMNs are a cystic lesion, rarely revealed by a large mass.

MR Prediction of Malignant Switch With the Cyst Fluid's T2 Value in Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Preliminary Study.

We investigated whether the malignant switch of intraductal papillary mucinous neoplasm (IPMN) of the pancreas can be predicted by using the T1ϱ, T2, and apparent diffusion coefficient (ADC) values of cyst fluid. We retrospectively analyzed the magnetic resonance (MR) images of 60 patients (26 males, 34 females, mean age 61 years) with branch-duct type and mixed-type IPMNs. The IPMNs were diagnosed clinically in 39 patients and histologically in 21 patients. The malignant potential was classified by MR imaging based on the international consensus guidelines for the management of IPMN established in 2017. Morphologically, 42 patients had "worrisome features" and three had "high-risk stigmata." Histologically, 14 lesions were diagnosed as low-grade dysplasia and seven as intermediate-grade dysplasia. The T1ϱ, T2, and ADC values of cyst fluid in each patient's largest cyst were measured on the same slice, avoiding solid components. Spearman's rank correlation test was used to determine the correlation between the morphological malignancy and the T1ϱ, T2, and ADC values. These values were also compared between the low-grade and intermediate-grade groups by Mann-Whitney U-test. There was a significant rank-correlation between the morphological classification and T2 value (p=0.04). The T2 value of the intermediate-grade group was significantly higher than that of the low-grade group (p=0.03). No significant correlations were morphologically or histologically obtained regarding T1ϱ and ADC. The T2 value of cyst fluid together with other MR-signs may be useful for predicting the malignant switch in IPMN of the pancreas.

An unusual presentation of intestinal type intraductal papillary mucinous neoplasm: A case report

An unusual presentation of intestinal type intraductal papillary mucinous neoplasm: A case report

Prediction of Malignancy in Main Duct or Mixed Type Intraductal Papillary Mucinous Neoplasms of the Pancreas

Introduction: Surgical indications of main-duct involved intraductal papillary mucinous neoplasms(IPMN), especially for main pancreatic duct(MPD) of 5-9mm, remain controversial. We aimed to predict malignancy risk of main-duct involved IPMN.

Combined Type IPMN: Radiographic versus Endoscopic Diagnosis

Introduction: Main duct and combined type pancreatic intraductal papillary mucinous neoplasm (IPMN) are associated with significant rates of high-risk pathology. The diagnosis is suggested radiographically, but endoscopic interventions are generally performed for confirmation. The goal of this study was to evaluate whether these interventions change management and increase accuracy in patients thought to have combined type IPMN based upon imaging alone. Methods: Patients thought to have main duct or combined type IPMN based on imaging were evaluated retrospectively. The outcome of endoscopic interventions performed on these patients was reviewed. Final pathology was available for patients who underwent resection. Results: 142 patients were felt to have main duct IPMN radiographically. 89 of those patients underwent EUS and 49 of these patients ultimately underwent resection. Final pathology showed main duct IPMN in 39 patients. 55 patients were felt to have combined type IPMN radiographically. 39 of these patients underwent EUS. 21/39 patients had an elevated CEA. 18/39 patients were felt to have combined type IPMN by endoscopic appearance. 24/55 patients ultimately underwent resection. Final pathology showed combined type (or main duct) IPMN in 23 patients with four harboring adenocarcinoma. Of the 24 patients that underwent resection, 11 had an elevated CEA and 12 were felt to have combined type IPMN by endoscopic appearance. Conclusions: Diagnosis of combined type IPMN on high-quality imaging is highly predictive of final pathology. Endoscopic interventions subject patients to additional procedural complications but often add little and may not improve accuracy.Tabled 1Main Duct IPMNRadiographic Diagnosis of Main Duct IPMN142EUS Diagnosis of Main Duct IPMN57/89Number Resected49Final Pathology Main Duct IPMN39/49 (80%) Malignancy6/49 (12%)Combined Type (Mixed-Type) IPMNRadiographic Diagnosis of Combined Type IPMN55EUS Diagnosis of Combined Type IPMN18/39Number Resected24Final Pathology Combined Type or Main Duct IPMN23/24 (96%) Malignancy4/24 (16%) Open table in a new tab Table: IPMN Diagnosis by Different Diagnostic Modalities.

Indicators of Malignancy and Invasive Cancer in Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Introduction: There are still many debates on the indication of surgical resection of IPMN. This study aims to validate malignant features detected in preoperative diagnosis of IPMN and establish selection criteria for appropriate surgical management. Method: Forty-eight IPMN patients who underwent surgical resection from January 2005 to December 2020 were enrolled. We assessed the correlation of factors with malignancy and searched for risk factors for invasive cancer. Results: Patients' characteristics; primary site (head/body and tail=28/20), type of IPMN (main pancreatic duct (MPD) type/ branched pancreatic duct (BD) type/ mixed type=9/20/19), malignancy (IPMA/high grade dysplasia/IPMC=17/11/10), jaundice (yes/no=1/47), diameter of main pancreatic duct >10mm (yes/no=17/31), enhanced nodule (yes/no=16/32), median cyst diameter >=30 mm (yes/no=20/28), thickened or contrast-enhanced septum (yes/no=19/29). Multivariate analysis showed the MPD diameter, enhanced nodule, and cyst size were indicators of malignancy. The malignancy rates of patients with two or more, one, and none of these factors were 100%/47%/24%, respectively. Multivariate analysis showed enhanced nodule and number of lesions (single or multiple) were indicators of invasive cancer. The invasive cancer rates of patients with two, one, and none of these factors were 80%/37%/7%, respectively. Conclusion: It was re-verified that the HRS factor and WF factors help indicate the presence of malignancy and invasiveness. Combinations of these findings will lead to more accurate predictions for malignancy and invasive cancer. Less invasive surgical procedures (limited lymphatic dissection, organ preservation) might be considered in patients with only a few HRS or WF factors.

Malignant potential and specific characteristics of pure main duct type intraductal papillary mucinous neoplasm

BackgroundAs the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN. MethodsFrom 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN. ResultsThe rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091). ConclusionsMeasurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.

Peroral Pancreatoscopy with Videoscopy and Narrow-Band Imaging in Intraductal Papillary Mucinous Neoplasms with Dilatation of the Main Pancreatic Duct.

Background/AimsEndoscopic evaluation of intraductal papillary mucinous neoplasms (IPMNs) is useful in determining whether the lesions are benign or malignant. This study aimed to examine the usefulness of peroral pancreatoscopy (POPS) in determining the prognosis of IPMNs. MethodsPOPS with videoscopy was performed using the mother–baby scope technique. After surgery, computed tomography/magnetic resonance cholangiopancreatography or ultrasonography and blood tests were performed every 6 months during the follow-up. ResultsA total of 39 patients with main pancreatic duct (MPD)–type IPMNs underwent POPS using a videoscope, and the protrusions in the MPD were observed in 36 patients. The sensitivity and specificity of cytology/biopsy performed at the time of POPS were 85% and 87.5%, respectively. Of 19 patients who underwent surgery, 18 (95%) patients had negative surgical margins and 1 (5%) patient had a positive margin. ConclusionsIn IPMNs with dilatation of the MPD, POPS is considered effective if the lesions can be directly observed. The diagnosis of benign and malignant lesions is possible depending on the degree of lesion elevation. However, in some cases, slightly elevated lesions may increase in size during the follow-up or multiple lesions may be simultaneously present; therefore, careful follow-up is necessary.

A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation

BackgroundEctopic pancreas is basically a benign disease and is not always necessary to be removed. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and intraductal papillary mucinous neoplasms (IPMNs) may develop even within ectopic pancreas. We recently encountered an extremely rare case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation.Case presentationA 71-year-old Japanese woman complained of epigastric pain. Computed tomography and upper gastrointestinal endoscopy showed an intramural cystic mass in the antrum of the stomach. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy did not give a definitive diagnosis, and the patient underwent resection of the lesion. Histology of the resected specimen showed that the gastric intramural lesion was ectopic pancreas. Moreover, the lesion contained dilated duct components with tubulo-villous epithelial proliferation consistent with pancreatic IPMN. Since the covering epithelial cells had highly atypical nuclei, the lesion was diagnosed as IPMN with high grade dysplasia. Immunohistochemistry showed that the IPMN component showed to be MUC2-, MUC5AC-, and CDX2-positive but MUC1- and MUC6-negative. Mutational analyses using genomic DNA revealed that the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys).ConclusionWe finally diagnosed this case as gastric ectopic pancreas accompanied by intestinal type IPMN with high grade dysplasia possessing GNAS mutation. Although there were 17 cases of ectopic pancreas with IPMN including 6 cases of gastric ones reported in the English literature, this is the first case of ectopic pancreas with IPMN which was proved to have GNAS mutation. Intimate preoperative examinations including imaging analyses and EUS-FNA biopsy/cytology are recommended to decide whether the lesion has to be resected or not even if they are not effective for getting the right diagnosis.

Imaging Features for Predicting High-Grade Dysplasia or Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Systematic Review and Meta-Analysis.

The consensus guidelines for branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas are mostly based on imaging features. This study aimed to determine imaging features and their diagnostic accuracy for predicting high-grade dysplasia (HGD)/malignancy in BD-IPMN, including mixed type. The PubMed, Embase, and Cochrane databases were searched, and data were extracted from relevant studies. As the main diagnostic accuracy index, diagnostic odds ratios (DORs) of imaging features for diagnosing HGD/malignancy in BD-IPMNs were pooled using the random-effects model. A bivariate random-effects approach was used to construct summary receiver operating characteristic curves for sensitivity and specificity estimation. The pooled DOR was the highest for the enhanced solid component/mural nodule (MN) (DOR, 12.21; 95 % confidence interval [CI], 6.14-24.27), followed by a main pancreatic duct (MPD) diameter of 10mm or greater (DOR, 7.93; 95 % CI, 3.02-20.83), solid component (DOR, 4.85; 95 % CI, 2.49-9.42), lymphadenopathy (DOR, 4.84; 95 % CI, 1.11-21.06), MN (DOR, 4.48; 95 % CI, 3.15-6.39), an MPD diameter of 5mm or greater (DOR, 3.69; 95 % CI, 2.62-5.19), abrupt change in MPD caliber with distal pancreatic atrophy (DOR, 2.65; 95 % CI, 1.66-4.24), thickened/enhancing walls (DOR, 2.38; 95 % CI, 1.57-3.60), and cyst size of 3cm or larger (DOR, 1.98; 95 % CI, 1.48-2.64). The largest area under the curve (0.89 and 0.95, respectively) and high specificity (0.95 and 0.98, respectively) also were found for enhanced solid component/MN and an MPD diameter of 10 mm or greater, albeit with low sensitivity (0.38 and 0.14, respectively). The aforementioned imaging features could aid in predicting HGD/malignancy of BD-IPMN. Furthermore, enhanced solid component/MN and an MPD diameter of 10mm or greater were the most important predictors of HGD/malignancy in BD-IPMN and should be considered as indications for surgery.

ASO Author Reflections: Imaging Predictors of High-Grade Dysplasia or Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Systematic Review and Meta-Analysis.

ASO Author Reflections: Imaging Predictors of High-Grade Dysplasia or Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Systematic Review and Meta-Analysis.

How to determine the surgical extent in patients with multifocal intraductal papillary mucinous neoplasm?

Intraductal papillary mucinous neoplasms (IPMNs) represent a heterogeneous disease spectrum encompassing benign-to-premalignant-to invasive lesions. IPMNs are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) believed to arise within a widespread neoplastic "field defect". The presence of patients with multifocal disease and/or development of additional lesions over time favorably supports a "field defect theory" and complicates surgical decisions. The international consensus Fukuoka guideline revealed that all pancreatic ductal epithelial cells are at risk of dysplastic change, as most typically shown in patients with multifocal IPMNs ranging from 18% to 41%. European guideline proposed that in patients with multifocal IPMNs, each lesion should be evaluated for surgical resection as a single entity. In multifocal IPMNs over the whole pancreatic parenchyma, it may be reasonable to perform partial pancreatectomy to remove the IPMNs with the highest oncological risk and perform life-long surveillance of the remaining lesions. Partial pancreatectomy should achieve margin negative resection with at least low-grade dysplasia margin. Even if all gross disease can be resected with partial pancreatectomy, there is still the unresolved question of the "field defect" and the extent to which it leaves the pancreatic remnant at risk for recurrent disease. Most pancreatic surgeons agree that the only way to definitively eliminate risk for PDAC is to perform total pancreatectomy (TP). Considering improved glycemic control and pancreatic enzyme replacement therapy, the threshold for TP should perhaps be lowered in patients with high risk as International consensus Fukuoka guideline recommended. Surgical indication of TP for multifocal IPMNs may be proposed in patients with diffuse main duct involvement, persistent high-grade dysplasia at the resection margin, and familial PDAC. Moreover, pre-operatively diagnosed pancreatobiliary type IPMNs may also serve as a potential target for TP. Surgical indication of TP should be decided on a case-by-case basis with a risk assessment of the patient considering goals of care and quality of life expectations.

Multifocal lesions in intraductal papillary mucinous neoplasms: Intraoperative pancreatic juice cytology

On radiological study, 25% to 41% of the patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have multifocal lesions. On the other hand, in pathological assessment, most of these patients had lots of micro premalignant lesions such as small IPMNs and pancreatic intraepitehrial neoplasms (PanINs) in the background pancreas, indicating that all the pancreas having IPMNs have a potential to develop multifocal lesions. There are 3 possible types of multifocal lesions in patients with IPMNs, namely multiple branch duct IPMNs (BD-IPMNs) by multicentric development, multiple main duct or mixed type IPMNs (MD- or Mix-IPMNs) by the mechanism of intraductal dissemination of the neoplastic cells [1,2], and the development of pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMNs [3,4]. Pancreatic juice cytology under endoscopic retrograde pancreatography is reported to leads early detection of concomitant PDAC during assessment of IPMNs [5], while it is often difficult to determine the location of malignant lesions when pancreatography and other imaging modalities cannot provide any significant abnormalities. Therefore, the role of intraoperative pancreatic juice cytology is to determine whether such lesions which are not detected by preoperative assessment might left in the remnant pancreas during partial pancreatectomy for IPMN. Previous report [6] demonstrated that in consecutive 48 patients who underwent intraoperative irrigation cytology in the remnant pancreas during partial pancreatectomy for IPMN, 5 patients had positive results and subsequently underwent additional resection of the pancreas. High-risk lesions including 4 PanIN-3 lesions and one invasive carcinoma were detected in all 5 additionally resected specimens. On the other hand, there might be possible patients who might have false negative result of intraoperative irrigation cytology [7] or peritoneal dissemination because of leakage of irrigation solution containing cells from high-risk lesions. In this presentation, roles and limitations of intraoperative pancreatic juice cytology will be discussed.

Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each type is associated with specific clinicopathological features. We aimed to uncover the molecular mechanisms underlying the development of these types of IPMN. We obtained 103 lesions of various types, including 49 gastric, 26 intestinal, 22 pancreatobiliary, and 6 oncocytic lesions, from 43 IPMNs, including 36 with multiple types. Comparative analysis was performed by targeted sequencing of 37 genes in different lesion types within each pancreas. Gastric-type low-grade lesions were observed in all 36 tumors with multiple types, with 245 mutations identified across all samples. The average number of mutations was significantly different between different lesion grades and types: 1.88 for low-grade lesions, 2.77 for high-grade lesions, and 2.38 for invasive lesions (p = 0.0067); and 1.96 for gastric-type lesion, 2.92 for intestinal-type lesion, 2.73 for pancreatobiliary-type lesion, and 2.17 for oncocytic-type lesion (p = 0.0163). Tracing of mutations between lesions containing multiple types in the same pancreas suggested three developmental pathways, denoted as "progressive", "divergent", and "independent". The progressive and divergent pathways indicate an ancestral lesion that was mostly gastric-type and low-grade may progress or diversify into lesions of other types and/or higher grades. The independent pathway suggests that some high-grade lesions of any type may develop independently. These findings suggest that gastric-type low-grade lesions have a risk of progression into high-grade lesions of other types. Therefore, low-grade gastric-type IPMNs should be under constant surveillance.

Radiomic nomogram based on MRI to predict grade of branching type intraductal papillary mucinous neoplasms of the pancreas: a multicenter study

BackgroundAccurate diagnosis of high-grade branching type intraductal papillary mucinous neoplasms (BD-IPMNs) is challenging in clinical setting. We aimed to construct and validate a nomogram combining clinical characteristics and radiomic features for the preoperative prediction of low and high-grade in BD-IPMNs.MethodsTwo hundred and two patients from three medical centers were enrolled. The high-grade BD-IPMN group comprised patients with high-grade dysplasia and invasive carcinoma in BD-IPMN (n = 50). The training cohort comprised patients from the first medical center (n = 103), and the external independent validation cohorts comprised patients from the second and third medical centers (n = 48 and 51). Within 3 months prior to surgery, all patients were subjected to magnetic resonance examination. The volume of interest was delineated on T1-weighted (T1-w) imaging, T2-weighted (T2-w) imaging, and contrast-enhanced T1-weighted (CET1-w) imaging, respectively, on each tumor slice. Quantitative image features were extracted using MITK software (G.E.). The Mann-Whitney U test or independent-sample t-test, and LASSO regression, were applied for data dimension reduction, after which a radiomic signature was constructed for grade assessment. Based on the training cohort, we developed a combined nomogram model incorporating clinical variables and the radiomic signature. Decision curve analysis (DCA), a receiver operating characteristic curve (ROC), a calibration curve, and the area under the ROC curve (AUC) were used to evaluate the utility of the constructed model based on the external independent validation cohorts.ResultsTo predict tumor grade, we developed a nine-feature-combined radiomic signature. For the radiomic signature, the AUC values of high-grade disease were 0.836 in the training cohort, 0.811 in external validation cohort 1, and 0.822 in external validation cohort 2. The CA19–9 level and main pancreatic duct size were identified as independent parameters of high-grade of BD-IPMNs using multivariate logistic regression analysis. The CA19–9 level and main pancreatic duct size were then used to construct the radiomic nomogram. Using the radiomic nomogram, the high-grade disease-associated AUC values were 0.903 (training cohort), 0.884 (external validation cohort 1), and 0.876 (external validation cohort 2). The clinical utility of the developed nomogram was verified using the calibration curve and DCA.ConclusionsThe developed radiomic nomogram model could effectively distinguish high-grade patients with BD-IPMNs preoperatively. This preoperative identification might improve treatment methods and promote personalized therapy in patients with BD-IPMNs.